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Diss Factsheets

Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientific publication with restrictions compared to Guideline Study (limited documentation)

Data source

Reference
Reference Type:
publication
Title:
The inhalation toxicity of phenylglycidyl ether: Reproduction, mutagenic, teratogenic, and cytogenetic studies
Author:
James B. Terrill1, K.P. Lee, Rudolf Culik, Gerald L. Kennedy Jr.
Year:
1982
Bibliographic source:
Toxicology and Applied Pharmacology, Volume 64, Issue 2, 30 June 1982, Pages 204-212

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Principles of method if other than guideline:
Male rats were exposed to either 0, 1, 5, or 12 ppm, 6 hours/day on 19 consecutive days.
These rats were mated with untreated females and the pups were examined for abnormalities. Litters were mated among each other and the next generation was examined for abnormalities.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
Name in the report: propane, 1,2-epoxy-3-phenoxy

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Source: Charles River
- Age at study initiation: 10 weeks
- Weight at study initiation: Males: ca. 260 g (females not reported)
- Diet (ad libitum): Purina rat chow
- Water (ad libitum)

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
Chamber atmospheres were generated by syringe driving the liquid EPP into a heated (310°C) tube. The tube was housed in an oven and constructed in such a way that the nitrogen stream (10 liters/minute) which swept the vapors through the tube was the same temperature as the delivery tube. The exit port of the tube was connected to the top of a 4.5 m3 exposure chamber. Room air at 1,500 liters/minute was also drawn into the chamber at this point.
Details on mating procedure:
- M/F ratio per cage: 1/3
- Length of cohabitation: 5 days
- Proof of pregnancy: no data
- After successful mating each pregnant female was caged individually
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Atmospheric samples were collected hourly in a midget impinger that contained 15 cc of 0:1 N NaOH in a 50:50 ethanol-water mixture. Analysis was performed by U.V. spectrophotometry at 270 nanometers.
Duration of treatment / exposure:
6h/day on 19 consecutive days (F0 males only)
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1, 5, 12 ppm
Basis:
analytical conc.
No. of animals per sex per dose:
8
Control animals:
yes, sham-exposed
Details on study design:
- Other:
- potential pregnancies were either terminated on the 18th day of gestation for examination of uterine contents or continued through parturition
- determination was dependent upon the number of litters sired per male:
-if three dams were impregnated, two were allowed to deliver and one pregnancy was terminated on the 18th day
-if two dams became pregnant, one was allowed to deliver, and one pregnancy was terminated
-if one litter was sired, it continued through to parturition

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily


DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule:

BODY WEIGHT: No data
- Time schedule for examinations:

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:

OTHER:
Oestrous cyclicity (parental animals):
No data
Sperm parameters (parental animals):
Parameters examined in [all/P/F1/F2] male parental generations: testis weight, epididymis weight
Litter observations:
STANDARDISATION OF LITTERS
- Performed @ birth: yes
- If yes, maximum of 8 pups/litter ; excess pups were randomly killed and discarded.

PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2] offspring:
[number and sex of pups, stillbirths, live births, weight gain, physical abnormalities]

GROSS EXAMINATION OF DEAD PUPS:
[no]
Postmortem examinations (parental animals):
SACRIFICE
Male animals (All surviving animals):
- F0 male animals were sacrificed following completion of the F0 mating trails
- 8 males of each week and group not employed during the F1 mating trials (12 weeks post weaning) and F1 parental males
- any animal appearing abnormal

Maternal animals (All surviving animals):
- each F0 female animal failing to conceive and each failing to deliver by the 23rd day of gestation
- 8 females of each week and group not employed during the F1 mating trials (12 weeks post weaning) and F1 parental females
- any animal appearing abnormal

GROSS NECROPSY
Yes

HISTOPATHOLOGY:
yes: reproductive organs of all the above mentioned animals (in addition, any tissue or organ noted abnormal during gross pathologic examination
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring not selected as parental animals were sacrificed at weaning and all F2 offspring were sacrificed 2 weeks post-weaning.

The pups were examined for physical abnormalities and developmental/behavioral anomalies at birth, at weaning and 2 weeks post-weaning prior to their sacrifice.
Statistics:
Fisher’s exact test: comparison of treated versus control females for the fertility index.
Mann-Whitney U test: comparison of treated versus control for the number of corpora lutea, number of implantations, pre- or postimplantation losses, number of litters with early or late resorptions, and number of viable fetuses.

(Significance at the 0.05 probability level.)
Reproductive indices:
Fertility index (number of matings (of 24) which resulted in pregancy), post implantation loss (number of implantations minus the number of viable fetuses)
Offspring viability indices:
Lactation index (number of pups alive at day 21 divided by the number retained at day 0)

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
yes one male rat from each treatment groups showed testicular atrophy
Other effects:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
the 1 and 12 ppm groups showed higher number of corpora lutea, implantations and viable fetuses than controls as result of biological variation rather than treatment; significantly lower number of females pregnant in the 12-ppm group

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
12 ppm (analytical)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Males where treated: nody weight, mortality, fertility

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings:
not specified

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
12 ppm (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: animals were not treated; body weight, growth, gross structural anomalies, gross pathology one male pup, derived of mating with a male rat exposed to 1 ppm, exhibited a patch of curly hair, mainly on the dorsal surface

Results: F2 generation

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
F2
Effect level:
12 ppm (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Gross Pathology

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion